1. Field of the Invention
The present invention relates to the fields of organic chemistry and chemotherapeutic compounds. Specifically, the present invention relates to 1-aryl(heteroaryl)pyrido[b]indoles or indole analogs thereof and their uses in treating cancers.
2. Description of the Related Art
More than half a million people die of cancer every year in the United States, making cancer the second leading cause of death in this country after heart disease. The total economic cost of cancer to the United States has been estimated at over $263 billion. Thus, the need for effective cancer therapies cannot be overstated.
The β-carboline scaffold and reduced derivatives thereof appear to be ‘privileged’ bioactive structures that occur in a variety of natural products with anticancer activity among other effects (1). For example, the ability of harmine to affect cyclin-dependent kinases and cancer cell proliferation has been described (2). Also, have reported a structure-activity relationship of tetrahydro-β-carbolines as cell cycle arresting agents and inducers of apoptosis has been reported (3). Tangutorine, a β-carboline alkaloid, was recently shown to be an inducer of p21 expression and abnormal mitosis in human colon cancer cells (4). Isostrychnopentam119(eine, an indolomonoterpenic alkaloid containing a tetrahydro-β-carboline moiety induces cell cycle arrest and apoptosis in human colon cancer cells (5).
There is still, however, a recognized need in the art for improved chemotherapeutics and cancer therapies. Specifically, the prior art is deficient in 1-aryl- or 1-heteroarylpyrido[b]indoles, for example substituted β-carbolines effective to inhibit cancer cell proliferation. The present invention fulfills this long standing need in the art.